4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide or Regorafenib is low molecular weight, orally available, inhibitor of multiple protein kinases, including kinases involved in tumour angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF, BRAFV600E), and the tumour microenvironment (PDGFR, FGFR). In preclinical studies regorafenib has demonstrated antitumour activity in a broad spectrum of tumour models including colorectal tumour models which is mediated both by its antiangiogenic and antiproliferative effects. Major human metabolites (M-2 and M-5) exhibited similar efficacies compared to Regorafenib both in vitro and in vivo models.
Regorafenib was approved USFDA, in 2012 and is marketed under the brand name Stivarga®, is an important chemotherapeutic agent useful for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies. These include fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy.
Regorafenib is chemically known as 4-[4-({[4-chloro-3-(trifluoromethyl) phenyl]carbamoyl} amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide (I). Regorafenib is a white to slightly pink or slightly brownish solid substance with the empirical formula C21H15ClF4N4O3 and a molecular weight of 482.82. Regorafenib is practically insoluable in water, dilute alkaline, solution, dilute acid solution n-heptane glycerine and toluene. It is slightly soluble in acetonitrile, dichloromethane, propylene glycol, methanol, 2-propanol, ethanol and ethyl acetate. It is sparingly soluble in acetone and soluble in PEG 400 (macrogol). Regorafenib is not hygroscopic.
Regorafenib is generically disclosed in U.S. Pat. No. 7,351,834, d specifically disclosed in U.S. Pat. No. 8,637,553. US '553 discloses process for the preparation of Regorafenib starting from 3-fluoro-4-nitrophenol. The process is as demonstrated below:

The present inventors has repeated the above process and found the following disadvantages:                Unwanted reactions are observed during the formation of Regorafenib due to the time in process.        Incomplete reactions were observed with excessive impurity formations due to incomplete conversion.        Removal of impurities from final product        
US 2010173953 disclose Regorafenib monohydrate and crystalline Form I of Regorafenib. This patent application further discloses that crystalline Form I of Regorafenib stated in this application is obtained as per the process disclosed in WO 2005009961 A2 (Equivalent to US '553). The compound obtained was having a melting point of 186-206° C.
This patent publication discloses a process for the preparation of Regorafenib monohydrate comprises dissolving Regorafenib Form I obtained as per WO '961 in acetone and the solution is filtered, followed by addition of water until precipitation, which was filtered and dried at room temperature
US 2010/0113533 discloses crystalline. Form II of Regorafenib, comprises dissolving Regorafenib Form I obtained as per WO '961 in ethyl acetate, the suspension was heated to 40-45° C., addition of isocyanate solution (isocyanate in ethyl acetate) and is cooled to room temperature to yield the crystals., which was filtered, washed with ethyl acetate and dried at room temperature.
US 2010/0063112 discloses Form III of Regorafenib, process comprises of heating Regorafenib monohydrate at 100° C. or 60 min, and further 15 min at 110° C., followed by cooling to room temperature.
As polymorphism has been given importance in the recent literatures owing to its relevance to the drugs having oral dosage forms due to its apparent relation to dose preparation/suitability in composition steps/bioavailability and other pharmaceutical profiles, stable polymorphic form of a drug has often remained the clear choice in compositions due to various reasons of handling, mixing and further processing including bioavailability and stability.
Exploring new process for these stable polymorphic forms which are amenable to scale up for pharmaceutically active/useful compounds such as 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl)}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide or Regorafenib may thus provide an opportunity to improve the drug performance characteristics of such products.
Hence, inventors of the present application report a process for the preparation of a stable and usable form of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide Regorafenib, which may be industrially amenable and usable for preparing the corresponding pharmaceutical compositions. The present invention provides an improved process for the preparation of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide or Regorafenib crystalline forms specifically for crystalline polymorphic forms Form I and Form III. Crystalline polymorphic forms of 4-[4-({[4-chloro-3-(trifluoromethyl) phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2 -carboxamide or Regorafenib obtained by the process of the present invention is non-hygroscopic and chemically stable and has good dissolution properties.
In view of the above and to overcome the prior-art problems the present inventors had now developed an improved process for the preparation of Regorafenib, using industrially feasible and viable process, with the use of industrially friendly solvents, which does not include tedious work up and time lagging steps.